精子染色质完整性对功能的影响及其检测方法研究进展

doi:10.16288/j.yczz.24-106

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Hereditas(Beijing) ›› 2024, Vol. 46 ›› Issue (7): 511-529.doi: 10.16288/j.yczz.24-106

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Research progress on the effect of sperm chromatin integrity on function and its detection methods

Daiyuan Liu¹^,²(), Zhaohui Zhang¹(), Xianjiang Kang³

1. Department of Reproduction Medicine, Baoding No.1 Central Hospital, Baoding 071000, China
2. Graduate School, Hebei Medical University, Shijiazhuang 050017, China
3. College of Life Science, Hebei University, Baoding 071000, China

Received:2024-04-21 Revised:2024-06-29 Online:2024-07-20 Published:2024-07-05
Supported by:
Baoding Science and Technology Plan Project(2341ZF280);Doctor Fund of Baoding No.1 Central Hospital

Abstract

Abstract:

Sperm chromatin not only carries genetic information such as paternal DNA, but also carries structural proteins, epigenetic information, and higher-order chromatin structures (such as matrix attachment regions and telomeres), etc. These information play an important role in embryonic development. This article mainly reviews the effects of these different information carried by sperm chromatin on sperm function and embryonic development and the research progress of related detection methods, in order to provide a theoretical basis and scientific diagnosis and treatment strategies for the etiology screening of clinical infertility, embryo arrest and recurrent miscarriage, so as to improve the pregnancy outcomes of natural conception and assisted reproduction. Keywords: sperm chromatin; epigenetics; sperm DNA damage; sperm function; higher-order chromatin structures

Key words: sperm chromatin, epigenetics, sperm DNA damage, sperm function, higher-order chromatin structures

Daiyuan Liu, Zhaohui Zhang, Xianjiang Kang. Research progress on the effect of sperm chromatin integrity on function and its detection methods[J]. Hereditas(Beijing), 2024, 46(7): 511-529.

Figures/Tables 4

Fig. 1

Table 1

Table 2

Table 3

Epigenetic modification of sperm chromatin assays"

表观遗传修饰	样本	方法	结果	参考文献
精子DNA甲基化	大鼠(Rattus norvegicus)	全基因组BS	孕前暴露于大麻的大鼠精子中可检测到甲基化的变化，并且子代DNA可检测到相关甲基化变化，这些变化在功能上与心脏扩大相关	[107]
	猪(Sus scrofa)	还原BS	不同水平的DNA片段化的精子细胞表现出相似的整体甲基化	[108]
	人(Homo sapiens)	MeDIP和NGS	检测到精子中有805个差异DNA甲基化区，可能作为父系后代自闭症易感性的生物标志物	[109]
	人(Homo sapiens)	ELISA	精子DNA甲基化水平与精子常规参数、精子染色质和DNA完整性相关	[110]
	山羊(Capra sibirica)	免疫组化	在长时间的慢速冷冻下(1~4小时) 可增加DNA甲基化	[111]
	金鱼/斑马鱼(Carassius auratus/Danio rerio)	LUMA	甲醇冷冻保存后金鱼精子的总体DNA甲基化没有改变，而二甲基亚砜和1,2 -丙二醇冷冻保存后DNA甲基化降低	[112]
	大盖巨脂鲤(Piaractus brachypomus)	酶促DNA甲基化分析	所有冷冻保护剂均可引起精子DNA甲基化的显著变化，并表现出更多的胚胎发育延迟和异常	[113]
	人(Homo sapiens)	高效液相色谱法	有缺陷的、凋亡的人类精子的产生与精子核DNA整体超甲基化的发生障碍相关	[114]
	人(Homo sapiens)	薄层色谱法和免疫荧光法	染色体结构异常携带者的染色质完整性的降低可能与精子DNA的低甲基化状态增加有关	[32]
	人(Homo sapiens)	DNA甲基化微阵列	男性年龄对ART结局产生负面影响的潜在机制是DNA甲基化的改变	[37]
精子组蛋白修饰	人(Homo sapiens)	苯胺蓝染色	部分圆头精子症组和完全圆头精子症组中组蛋白含量无差别	[115]
	铜藻(Sargassum horneri)	蛋白印记和质谱检测	第一次在动物以外的谱系中发现组蛋白H1的存在	[116]
	人(Homo sapiens)	蛋白印记和染色质免疫沉淀	TH2B参与精子染色质致密化过程	[117]
精子组蛋白修饰	人(Homo sapiens)	免疫细胞化学	在正常成熟人类精子中观察到组蛋白甲基化的异质性存在，没有观察到组蛋白乙酰化(H3K4Ac和H4K5Ac)	[118]
精子组蛋白修饰	牛(Bovine)	免疫荧光和蛋白印迹	TH2B可能参与催化组蛋白的转化	[119]
精子染色质重塑	人(Homo sapiens)	苯胺蓝染色和CMA3	在复发性流产夫妇的男性伴侣中，阿尔法硫辛酸治疗可减轻精子DNA损伤和脂质过氧化，同时增强精子总活力和染色质致密化	[120]
精子染色质重塑	野猪(Sus scrofa)	染色质二硫键检测法	猪精子冷冻储存会增加精子二硫键的破坏	[121]

Table 3

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方法	检测指标	优点	缺点	参考文献
SCSA	用吖啶橙进行染色，计数红色荧光精子比例	高效、易于标准化，有临床阈值	间接检测DNA损伤，敏感性低	[22]
TUNEL	用脱糖核苷酸标记存有断裂的DNA，至少检测200个精子	直接评估DNA的SSBs/DSBs，特异性高	耗时长，步骤复杂，需自己设置阴阳对照与阈值	[23]
Comet assay	精子尾部带荧光彗星样精子比例	直接评估DNA的SSBs/DSBs，敏感性与特异性高	耗时长，步骤复杂，技术人员需有较高专业知识	[24]
SCD	计数小或无晕精子比例	经济高效，准确度高，易于临床推广	间接评估DNA损伤，主观性强	[2]
8-OHdG检测法	用酶消化DNA，分别检测8-OHd G和d G，结果以OHd G/105d G表示	用来辅助评估DNA氧化损伤程度	步骤复杂，成本高，不利于临床推广，需要技术人员有较高的专业水平	[25]
γH2AX检测法	用荧光抗体标记γH2AX ，用荧光显微镜或流式细胞仪观察，计数荧光精子比例	结果客观，荧光显微镜能观察DNA断裂位点	步骤复杂，成本高，不利于临床推广，需要技术人员有较高的专业水平	[26]
TB检测法	受损的DNA更易与TB染料结合，损伤越严重，染色越深，计算头部深蓝色精子比例	简便、快捷，适用于临床实验室推广	人为计数，主观性强	[27]
拉曼光谱检测技术	激光照射，采集并分析光谱信号强度	无创检测，灵敏度高，效率高	需要专业仪器，需要技术人员有较高的专业水平	[28]
ORP检测法	通过评估样本中的氧化剂和还原剂的比例，直接测量氧化应激程度	结果重复性高	需要专业系统：MiOXSYS System，要求技术人员有较高的专业水平	[29]

因素	异常基因	参考文献
高龄	DRD346、HTR2A47、GRIN1、SYNGAP1、DEFB126、DLGAP2、FGF11、MYOF、SNRPN	[37,41]
吸烟与酒精	LINE-1、MEST、GNAS、P16、F2RL3、AHRR	[39,42]
PM2.5	PRR16、TJP2、NFATC1、APOA5、ZFP945、GSE1	[43]
双酚A	LINE-1、ACHE、PPP2R3C、MLH1、CHD2、SPATA12、SPATA20、TFPI2、FOXF1、SALL1、CDKN1C、HOXC4、ATP5G3、NDUFV2、ASAH1、RAD23B、CUL3、HSPA1L、UBAP2	[44⇓~46]

Research progress on the effect of sperm chromatin integrity on function and its detection methods

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